Understanding the structure of bone is the foundation upon which advances can be made in determining the processes involved in its formation, and the factors responsible for its malformation. It is proposed to substantiate and evaluate our recently discovered structural model of bone, in which the crystals in individual lamellae are primarily arranged in parallel layers. Of particular interest, will be the comparisons between the structures of bones performing different function sin the same animal (the rat), and between Haversian and non-Haversian bone, as well as the determination of the stages of crystal growth in association wit collagen fibrils (mineralizing turkey tendon). Both electron diffraction and imaging in the transmission electron microscope (TEM) will be extensively used, as well as scanning electron microscopy. The transition will then be made to probing processes of crystal formation in bone, using a novel "all-cryo" methodology for immunochemical mapping of various non-collagenous acidic macromolecular constituents in relation to crystal formation. A key question will be the presence of such components at the nucleation site. Cryo-sectioned mineralized tissues will be studied unstained and "hydrated" in the vitrified state using the TEM. The structural information from normal bones will be compared with that from bones suffering pathology, in order to identify any significant differences, and hopefully relate these to the manner in which the tissue malfunctions.